Vashishtha, M., Ng, C.W., Yildirim, F., Gipson, T.A., Kratter, I.H., Bodai, L., Song, W., Lau, A., Labadorf, A., Vogel-Ciernia, A., Troncosco, J., Ross, C.A., Bates, G.P., Krainc, D., Sadri-Vakili, G., Finkbeiner, S., Marsh, J.L., Housman, D.E., Fraenkel, E., Thompson, L.M. (2013). Targeting H3K4 trimethylation in Huntington disease.  Proc. Natl. Acad. Sci. U.S.A. 110(32): E3027--E3036.

FBrf0222382

Research paper

Transcriptional dysregulation is an early feature of Huntington disease (HD). We observed gene-specific changes in histone H3 lysine 4 trimethylation (H3K4me3) at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD.

PMC3740882 (PMC) (EuropePMC)